OBJECTIVE: Vitamin A and related compounds (retinoids) have been shown to have preventive and therapeutic effects on several types of tumors in the intact animal, to prevent carcinogen-induced hyperplasia in organ culture, and to restore some functions of normalcy to transformed and/or tumor cells in culture. Vitamin A deficient animals are also more susceptible to carcinogens and may be more prone to development of spontaneous tumors. The overall objective is to study the effects of retinoids on transformed and tumor cells. Specifically we are studying the effects of retinoids on: a) Tumor and transformed cells in culture; 1) to establish in vitro systems for comparing the efficacy of various retinoids and to be able to predict modifications of structure which may increase the anti-tumor effects, 2) to compare and determine competitive effects of various retinoids, 3) to study the molecular basis for the action of retinoids on tumor and transformed cell growth, 4) to determine why certain tumors and transformed cells are susceptible and others resistant to retinoid treatment. b) Tumor cells in the intact animal; 1) to correlate in vitro findings with in vivo effects and 2) to establish optimal conditions for treatment. APPROACH: Some of the approaches are listed above. Currently we are employing HeLa and L-929 cells as susceptible cells for retinoid action. These cells revert to normal phenotype with respect to growth control when treated with retinoids, especially retinoic acid and its analogues. These normal functions which seem to be restored include density dependent growth and anchorage dependent growth controls. In suspension cultures, retinoic acid induces a G1 cell cycle block which is reversible. We are currently trying to determine the exact time in the cell cycle that the block is imposed and trying to determine the molecular basis for the induced block.